Infectious diseases and microbiology continue to be areas of pivotal importance in health care research. Infection remains a major cause of mortality worldwide and poses serious problems of both individual and public health concern in the United States. Antibiotic resistance occurs at an alarming and increasing rate among all classes of mammalian pathogens. Moreover, diseases once thought to be near eradication from the developed world?for example, tuberculosis, cholera, and rheumatic fever?have rebounded with renewed intensity. Currently in its 40th year, the Infectious Disease and Basic Microbiological Mechanisms training program maintains as its primary goal the training of scientists who have a career goal of solving medically relevant problems and who elect rigorous laboratory or epidemiologic training in any of the Harvard adult infectious disease programs or other Harvard-based institutions participating in this program. Over the past 40 years, the program has successfully trained leaders in academic medicine and investigators who have made important contributions to the field. In this competing renewal application, we propose an additional five years of funding and to maintain the training program at its current level of seven postdoctoral trainees slots per year. We will use these slots to provide support directly to selected infectious disease physician fellows during mentored research, and to also provide support to selected Ph.D. trainees in Harvard Medical School infectious disease and microbiology laboratories focused on areas that have significant clinical relevance, so as to support the rich research training environment for physician-scientists within these laboratories and to provide these Ph.D. trainees intensive exposure to medically-trained clinically-active researchers. Training will include a minimum of two years of mentored research with hands-on in-laboratory training, appropriate advanced non-degree-granting post-graduate coursework, attendance and participation of trainees at regular meetings and seminars of direct relevance to infectious disease and microbiology research, including an annual training program retreat, and instruction in the preparation of competitive proposals for funding, with a particular emphasis on applications for K and other career development awards, including foundation awards. The specific aims are as follows: 1. To acquire sufficient training in basic laboratory or epidemiologic techniques and approaches to conduct effective cutting-edge research into relevant infectious disease problems; 2. To foster the creation of important scientific contributions by means of strong and longitudinal mentorship by program faculty; and 3. To develop a primary research focus and a broad understanding of infectious diseases and microbiology, so as to both enable novel interdisciplinary research and lead to independence.!